magistrsko delo
Tjaša Leban (Author), Toni Petan (Mentor)

Abstract

Lipidne kapljice (LK) omogočajo rakavim celicam prilagajanje na stresne razmere v mikrookolju. Biogenezo LK poganja sinteza trigliceridov, ki jo posredujeta diacilglicerol aciltransferazi (DGAT) 1 in 2. Naše nedavne raziskave so pokazale, da so LK poleg vzdrževanja energetske in redoks homeostaze pomembne tudi pri proizvodnji pro-tumorigenih lipidnih mediatorjev, katerih sintezo inducira fosfolipaza A2 (PLA2). Vprašali smo se, ali inhibicija encimov DGAT1 in DGAT2 vpliva na proliferacijo in migracijo rakavih celic in ali je učinek človeške sekretorne fosfolipaze A2 iz skupine X (hGX sPLA2) na proliferacijo rakavih celic odvisen od LK. Pokazali smo, da je bila biogeneza LK pri celicah pljučnega raka A549 in celicah raka dojke MDA-Luc-RFP znižana s kombinirano inhibicijo encimov DGAT1 in DGAT2, kar je povzročilo zmanjšanje proliferacije in migracije rakavih celic. Tretiranje s hGX sPLA2 je povzročilo tvorbo LK in povečalo stopnjo proliferacije pri obeh celičnih linijah, vendar smo lahko njen učinek preprečili s kombinacijo obeh inhibitorjev DGAT. Ugotovili smo tudi, da je utišanje citosolne fosfolipaze A2 iz skupine IVA (cPLA2α), ki poganja proizvodnjo eikozanoidov, zmanjšalo proliferacijo celic A549 in preprečilo proliferativni učinek hGX sPLA2. V delu smo pokazali, da biosinteza trigliceridov in biogeneza LK spodbujata proliferacijo rakavih celic in posredujeta pri mitogenih učinkih PLA2 iz skupine X in IVA.

Keywords

biotehnologija;lipidne kapljice;rak dojke;DGAT;rak pljuč;proliferacija;fosfolipaza;inhibitor diacilglicerol aciltransferaz;

Data

Language: Slovenian
Year of publishing:
Typology: 2.09 - Master's Thesis
Organization: UL BF - Biotechnical Faculty
Publisher: [T. Leban]
UDC: 606:616-006.6:601.4:577.21(043.2)
COBISS: 135998979 Link will open in a new window
Views: 28
Downloads: 10
Average score: 0 (0 votes)
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Other data

Secondary language: English
Secondary title: ǂThe ǂeffect of diacylglycerol acyltransferase inhibitors on cancer cell growth
Secondary abstract: Lipid droplets (LD) enable cancer cells to adapt to stressful conditions in their microenvironment. LD biogenesis is driven by triglyceride synthesis mediated by diacylglycerol acyltransferases (DGAT) 1 and 2. Our recent studies have shown that apart from their role in energy and redox homeostasis, LDs are also important for the production of pro-tumorigenic lipid mediators, also mediating phospholipase A2 (PLA2)-induced lipid mediator production. We asked whether the inhibition of DGAT1 and DGAT2 enzymes affects cancer cell proliferation and migration and whether the effect of human group X secreted phospholipase A2 (hGX sPLA2) on cancer cell proliferation depends on LDs. We show that LD biogenesis in A549 lung cancer and MDA-Luc-RFP breast cancer cells was supressed by combined inhibition of DGAT1 and DGAT2 enzymes, leading to reduced cancer cell proliferation and migration. Treatments with hGX sPLA2 induced LD formation and increased the rate of proliferation in both cell lines, but its effects were reversed by the combination of both DGAT inhibitors. We also found that knockdown of the intracellular group IVA cytosolic PLA2 (cPLA2α), the canonical enzyme driving eicosanoid production, decreased the proliferation of A549 cells and suppressed the proliferative effect of the sPLA2. This work demonstrates that triglyceride biosynthesis and LD biogenesis drive cancer cell proliferation and also mediate the mitogenic effects of group X and group IVA PLA2s.
Secondary keywords: biotechnology;lipid droplets;breast cancer;lung cancer;proliferation;phospholipase;
Type (COBISS): Master's thesis/paper
Study programme: 0
Embargo end date (OpenAIRE): 1970-01-01
Thesis comment: Univ. v Ljubljani, Biotehniška fak., Študij biotehnologije
Pages: 1 spletni vir (1 datoteka PDF (XI, 46 f., [11] f. pril.))
ID: 17509555